"The Market Saw blog is creating ripples today by stating that they've confirmed that the Lizard is the villain of the piece. Further, they're stating that the Lizard is the only villain in the film."

I don't see this happening. Add the Chameleon (Bruce Campbell) & Kraven (Bruce Campbell?) and now you've go something. If you want to have some fun toss in Vermin too, for Kraven to hunt down.

After that, wrap up the franchise with the Sinister Six story in Spider-man 5 (any 6 Spidey villains - some old, some new - will do as long as Electro's in there as the heavy) and then reboot it in a few years.